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Fig. 6 | Genome Biology

Fig. 6

From: Cis and trans effects differentially contribute to the evolution of promoters and enhancers

Fig. 6

Forty percent of regulatory pairs show evidence of compensation between cis and trans effects. a Example of a compensatory cis-trans effect (left) and a directional cis-trans effect (right). Effect sizes > 0 indicate higher activity in the mouse sequence or cellular environment whereas effect sizes < 0 indicate higher activity in the human sequence or cellular environment. b Percent of regulatory element pairs across biotypes with directional cis/trans effects (blue) and compensatory cis/trans effects (gray), broken up by conservation status. Only pairs with both cis and trans effects are considered, and the total number in each group is shown. c Schematic showing overview of how native effects are defined. d Volcano plot of native effect sizes for orthologous regulatory element pairs (black) compared to null differential controls (gray). Horizontal line depicts an empirical FDR cutoff of 0.1, calculated using null differential controls (see the “Methods” section). e Absolute native effect sizes for sequences showing compensatory cis-trans effects compared to directional cis-trans effects. p value shown is from a one-sided Mann-Whitney test. f Schematic showing the analysis outlined in gi. Darker triangles depict TADs as defined by Dixon et al. [34]. Elements in the MPRA include both gene and eRNA TSSs. g Number of transcribed enhancers (mean between human and mouse tiles) within the same TAD as given elements in the MPRA, broken up by conservation status. Only pairs with both cis and trans effects are considered, and the number in each group is shown. p values shown are from a two-sided Mann-Whitney test. h Example of Otsu’s method applied to threshold transcribed enhancers into those that are “redundant” (based on CAGE expression correlation) and those that are not. In this example, 49 transcribed enhancers are higher than the threshold (dashed line) and are therefore considered redundant with the element in the MPRA. i Number of redundant transcribed enhancers within the same TAD (mean between human and mouse tiles) as defined by Otsu’s method, broken up by conservation status. Only pairs with both cis and trans effects are considered, and the number in each group is shown. p values shown are from a two-sided Mann-Whitney test

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